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Genetic deletion of PDE10A selectively impairs incentive salience attribution and decreases medium spiny neuron excitability
- Source :
- Behavioural brain research. 268
- Publication Year :
- 2013
-
Abstract
- The striatum is the main input structure to the basal ganglia and consists mainly out of medium spiny neurons. The numerous spines on their dendrites render them capable of integrating cortical glutamatergic inputs with a motivational dopaminergic signal that originates in the midbrain. This integrative function is thought to underly attribution of incentive salience, a process that is severely disrupted in schizophrenic patients. Phosphodiesterase 10A (PDE10A) is located mainly to the striatal medium spiny neurons and hydrolyses cAMP and cGMP, key determinants of MSN signaling. We show here that genetic depletion of PDE10A critically mediates attribution of salience to reward-predicting cues, evident in impaired performance in PDE10A knockout mice in an instrumentally conditioned reinforcement task. We furthermore report modest impairment of latent inhibition in PDE10A knockout mice, and unaltered prepulse inhibition. We suggest that the lack of effect on PPI is due to the pre-attentional nature of this task. Finally, we performed whole-cell patch clamp recordings and confirm suggested changes in intrinsic membrane excitability. A decrease in spontaneous firing in striatal medium spiny neurons was found. These data show that PDE10A plays a pivotal role in striatal signaling and striatum-mediated salience attribution.
- Subjects :
- Male
Action Potentials/physiology
Patch-Clamp Techniques
Inhibition (Psychology)
Action Potentials
Striatum
Biology
Neuropsychological Tests
Medium spiny neuron
Behavioral Neuroscience
Reward system
Latent inhibition
Reward
Basal ganglia
Conditioning, Psychological
Avoidance Learning
Animals
Attention/physiology
Attention
GABAergic Neurons
Prepulse Inhibition/physiology
Phosphoric Diester Hydrolases/deficiency
Prepulse inhibition
Medicine(all)
Mice, Knockout
Phosphoric Diester Hydrolases
Prepulse Inhibition
Avoidance Learning/physiology
Taste Perception
GABAergic Neurons/physiology
Mice, Inbred C57BL
Conditioning (Psychology)/physiology
Inhibition, Psychological
nervous system
Reinforcement (Psychology)
Incentive salience
Taste Perception/physiology
PDE10A
Cues
Neuroscience
Reinforcement, Psychology
Subjects
Details
- ISSN :
- 18727549
- Volume :
- 268
- Database :
- OpenAIRE
- Journal :
- Behavioural brain research
- Accession number :
- edsair.doi.dedup.....0e3228b0e459ef857e9f6e92afa6d1f1